Compositions for Enhancing Sexual Responsiveness

ABSTRACT

A topical composition which enhances sexual responsiveness of a mammal is disclosed. An effective dosage of a peripheral vasodilator, an absorption enhancer and, optionally, a vasoconstrictor and an alpha receptor blocker are combined with a pharmaceutically-acceptable topical vehicle to produce the composition. The compositions are applied topically to the penis or labia majora and minora pudenda to enhance erection or vasocongestion.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.10/775,574, filed Feb. 9, 2004, now U.S. Pat. No. 7,214,390, whichclaims priority under 35 U.S.C. §119(e) to U.S. Provisional PatentApplication Ser. No. 60/445,624, filed Feb. 7, 2003. These patentapplications are incorporated herein, in their entirety, by thisreference.

FIELD OF THE INVENTION

The invention relates to a topically-administered compositions for theenhancement of sexual responsiveness in mammals.

BACKGROUND OF THE INVENTION

The male sexual response includes the filling of vascular channels thatare empty in the flaccid penis, with blood at pressures approachingsystemic levels. Erection occurs when the arteriolar and sinusoidalsmooth muscles of the vessels within the corpora relax, thus loweringresistance in these channels and allowing arterial blood to surge intothe penis. Exit of the arterial blood is simultaneously impeded by anincrease in venous resistance. Further distention of the sinusoids isrestrained by the minimally distensible tunica albuginea that raises thepressure further and also restricts venous outflow. Thus, the corporacavernosa and corpus spongiosum can be filled with blood and the peniscan be erect with little demand on cardiac output. These vascularchanges that occur during erection are thought to be controlled byvasoactive intestinal polypeptide, perhaps aided by alpha-adrenergicblockade, acetylcholine and nitric oxide.

The female sexual response cycle is typically divided into four phasesincluding desire, excitement, which includes physiological changes suchas vasocongestion in the pelvis, vaginal lubrication, and expansion andswelling of the external genitalia, orgasm, and resolution. Disorders offemale sexual desire or response are estimated to affect from 30 to 50percent of the adult female population. These disorders may have avariety of causes including psychogenic etiologies, anatomicaldisorders, drug-induced disorders, diabetes mellitus, post-surgicaldisorders, atherosclerosis, post-traumatic disorders, as well asendocrine etiologies. Depending upon the etiology of the disorder,effective treatment may be had by overcoming any boundaries to thephysiological changes that take place during excitement includingvasocongestion. Thus, in certain cases, it may be possible to enhancethe female sexual response by stimulating vasocongestion.

There are a wide variety of pharmacological agents used for theenhancement of erection and treatment of sexual dysfunction and aspro-libido agents. Some examples include: serotonin receptor agonistsand antagonists (see, e.g., EP 385,658; WO 94/15,920; GB 2,248,449; andGB 2,276,165), dopamine receptor agonists (see, e.g., WO 93/23,035; WO94/21,608; Pomerantz S. M., Pharmacol. Biochem. Behav. 39:123-128, 1991;and Ferrari F. et al. Psychopharmacology 113:172-176, 1993); adrenergicreceptor agonists (see, e.g., WO 95/13,072; EP 611,248; U.S. Pat. No.5,229,387; and WO 92/11,851); inhibitors of phosphodiesterase (see,e.g., DE 4,338,948; and WO 94/28,902); histamine receptor agonists (see,e.g., U.S. Pat. Nos. 4,013,659; 4,126,670; 4,767,778; WO 91/17,146; U.S.Pat. No. 5,047,418; and EP 0,458,661); neuropeptide Y antagonists (see,e.g., WO 95/00,161); angiotensin II receptor antagonists (see, e.g., EP577,025); cholinesterase inhibitors (see, e.g., U.S. Pat. Nos.5,177,070; and 4,633,318); combinations of agents with the differenttypes of biological activity (see, e.g., U.S. Pat. No. 5,145,852; and WO95/05,188); derivatives of vasoactive intestinal peptide (see, e.g.,U.S. Pat. No. 5,147,855; EP 540,969; and EP 463,450); prostaglandins(see, e.g., WO 93/00,894; and EP 459,3770); antidepressants andantipsychotics (see, e.g., U.S. Pat. No. 4,931,445; GB 2,448,449; andNaganuma et al. Clin. Exp. Pharm. Physiol. 20:177-183, 1993); nitricoxide donors (see, e.g., WO 92/21,346; DE 4,305,881; DE 4,212,582; andWO 94/16,729); calcitonin gene related peptide (see, e.g., Steif, C. G.et al., Urology, 41:397-400, 1993); and androgens (see, e.g., JP06,211,675; HU 62,473; and WO 94/16,709). Unfortunately, many or all ofthese pharmacological agents are associated with adverse effectsincluding aggravation or induction of schizophrenia, serotonin syndrome,central nervous system and endocrine system dysfunction, pain,echytomosis and priapism.

Accordingly there is a need in the art to identify new pharmacologicalagents or compositions which are useful for enhancement of the sexualresponse in mammals.

SUMMARY OF THE INVENTION

One embodiment of the present invention provides a topical compositioncomprising at least one active ingredient including methyl nicotinate,yohimbe, L-arginine in a pharmaceutically-acceptable topical vehicle.These compositions may also include as least one additional activeingredient including muira puama, catuaba, maca extract, and sawpalmetto. In a preferred embodiment, the composition contains methylnicotinate, yohimbe, L-arginine, muira puama, catuaba, maca extract, sawpalmetto, nettles and zinc. In another preferred embodiment, thecomposition contains methyl nicotinate, L-arginine, muira puama,catuaba, maca extract, nettles and zinc.

In a particularly preferred embodiment, the compositions containsbetween about 0.1% and about 5% methyl nicotinate, between about 5 dropsand about 50 drops of yohimbe extract, between about 0.3% and about 1.5%L-arginine; between about 1 drop and about 30 drops of muira puamaextract per four ounces of composition, between about 1 drop and about30 drops of catuaba extract per four ounces of composition, betweenabout 1 drop and about 30 drops of maca extract per four ounces ofcomposition, and between about 1 drop and about 30 drops of saw palmettoextract per four ounces of composition in a pharmaceutically-acceptabletopical vehicle.

Preferably, the compositions of the present invention are formulated ina topical lotion containing aloe and vitamin E.

Another preferred embodiment is a condom having an internal surfacecoated with one of the topical compositions of the present invention.

In another particularly preferred embodiment of the present inventionthe topical composition contains about 1% methyl nicotinate, about 25drops of yohimbe extract, about 8 mg/cm³ of L-arginine, about 12 dropsof muira puama extract, about 12 drops of catuaba extract, about 12drops of maca extract, and about 12 drops of saw palmetto extract in apharmaceutically-acceptable water-based topical vehicle containing aloeand vitamin E.

In another particularly preferred embodiment of the present invention,the topical composition contains about 1% methyl nicotinate, about 8mg/ml of L-arginine, about 12 drops of muira puama extract, about 12drops of catuaba extract, and about 12 drops of maca extract, in apharmaceutically-acceptable water-based topical vehicle containing aloeand vitamin E.

DETAILED DESCRIPTION OF THE INVENTION

As used herein, the transitional phrases “comprising”, “consistingessentially of” and “consisting of” define the scope of the appendedclaims with respect to what un-recited additional components, if any,are excluded from the scope of the claim. The term “comprising” isintended to be inclusive or open-ended and does not exclude additional,un-recited elements or method steps. The phrase “consisting of” excludesany element, step, or ingredient not specified in the claim. The phrase“consisting essentially of” limits the scope of a claim to the specifiedmaterials or steps and those that do not materially affect the basic andnovel characteristic(s) of the claimed invention. All compositions orformulations identified herein can, in alternate embodiments, be morespecifically defined by any of the transitional phrases “comprising”,“consisting essentially of” and “consisting of.”

The two most important denominators to the erection process and penissize are blood flow and vessel size. The compositions of the presentinvention are formulated with a combination of active ingredients thatenhance blood flow to the area applied thereby resulting in erection orvasocongestion. The active ingredients in these compositions aid thebody in the production of nitric oxide via the essential amino acidL-arginine. Additionally, these compositions function as powerfulvasodilators using yohimbe, and methyl nicotinate to increasecirculation, discourage clot formation, and reinforce the walls of thecapillaries allowing for bigger, thicker blood vessels. Thesephysiological actions are believed to be useful for the treatment ofsexual dysfunction resulting from circulatory disorders. Additionally,these physiological actions are believed to strengthen blood vesselwalls of the penis resulting in erectile enhancement. Further, herbalingredients in these compositions can act to promote and enhance desirefunctioning as pro-libido agents.

The compositions of the present invention contain one or more of thefollowing active ingredients: methyl nicotinate, yohimbe extract, panaxginseng, L-arginine, muira puama, catuaba bark, maca, and saw palmetto.

Methyl nicotinate is rubefacient and counterirritant for the relief ofaches and pains in muscles, tendons, and joints. When applied to theskin, methyl nicotinate causes vasodilation of the surrounding bloodvessels producing a feeling of warmth. This sensation competes with, andto some extent blocks, pain in underlying muscles and joints, since bothfeelings are conveyed by the same nerves. The compositions of thepresent invention may contain between about 0.1% and about 5% methylnicotinate. Preferably, the compositions of the present inventioncontain between about 0.5% and about 2% methyl nicotinate. Mostpreferably, the compositions of the present invention contain about 1%methyl nicotinate. Suitable sources of methyl nicotinate for use incompositions of the present invention are available commercially. Forexample, methyl nicotinate is available commercially from AraerChemicals.

Yohimbe is a vasodilator used as a sensual stimulant for healthy men andwomen and to treat organic impotence. Yohimbe is thought to stimulatethe pelvic nerve ganglia and is thus useful for the treatment oferection problems. Effects may include increased libido, increasedsensation and increased stamina. The compositions of the presentinvention may include yohimbe extract prepared by extracting the yohimbefor one ounce of a plant material containing the herb into two ounces ofa suitable liquid. Typically the extraction liquid is water or analcohol. Prepared in this manner, compositions of the present inventionmay contain between about 5 drops and about 50 drops of the yohimbeextract in 120 cm³ of the topical composition of the present invention.Preferably, the compositions of the present invention contain betweenabout 15 drops and about 35 drops of the yohimbe extract in four ouncesof the topical composition. Most preferably, the compositions of thepresent invention contain about 25 drops of the yohimbe extract in fourounces of the topical composition. Herbal extracts containing yohimbethat are suitable for use in formulating compositions of the presentinvention are available commercially. For example, an herbal blendcontaining yohimbe that is suitable for use in compositions of thepresent invention is commercially available from Nature's Alternative.

Panax ginseng is an herb thought to be an immune stimulant. Ginseng hasa high content of the Rg1 group of ginsenosides which cause an increasein motor activity. It acts on the adrenal and pituitary glands and isthought to improve response to stress, increase mental and physical workcapacity, increase concentration and mental activity, enhance mentalacuity and intellectual and physical performance and benefit the immunesystem. The compositions of the present invention may include ginsengextract prepared by extracting ginseng from one ounce of a plantmaterial containing the herb into two ounces of a suitable liquid.Typically the extraction liquid is water or an alcohol. Prepared in thismanner, compositions of the present invention may contain between about1 drop and about 30 drops of ginseng extract in four ounces of thetopical composition. Preferably, the compositions of the presentinvention contain between about 5 drops and about 20 drops of ginsengextract in four ounces of the topical composition. Most preferably, thecompositions of the present invention contain about 12 drops of ginsengextract in four ounces of the topical composition. Herbal extractscontaining ginseng that are suitable for use in formulating compositionsof the present invention are available commercially. For example, anherbal blend containing ginseng that is suitable for use in compositionsof the present invention is commercially available from Nature'sAlternative.

L-arginine is an essential amino acid with vasodilatory properties.L-arginine is the primary nutrient that allows the body to create nitricoxide, which helps regulate every physiologic function in the body.L-arginine has been shown to reduce blood pressure, improve heartfunction, circulation, lower cholesterol, improve immune systemresponse, wound healing, open airways in asthma and help with malesexual function. When arginine is introduced into the body, it interactswith the enzyme nitric oxide synthase which replaces a nitrogen moleculeon arginine with an oxygen atom forming nitric oxide. The compositionsof the present invention may contain between about 100 mg and about 400mg of L-arginine per ounce of the topical composition. Preferably, thecompositions of the present invention contain between about 200 mg andabout 300 mg of L-arginine per ounce of the topical composition. Mostpreferably, the compositions of the present invention contain about 240mg of L-arginine per ounce of the topical composition. L-argininesuitable for use in formulating compositions of the present invention isavailable commercially. For example, a commercial source of L-argininethat is suitable for use in compositions of the present invention iscommercially available from T. J. Clark.

Muira puama is a botanical isolated from a tree that grows in the rainforests of Brazil. Used as a mild tonic, this herb is thought to beuseful in treating the symptoms of nervous problems and disorders suchas neurasthenia, neuralgia and nervous depression. The compositions ofthe present invention may include muira puama extract prepared byextracting one ounce of muira puama plant material into two ounces of asuitable liquid. Typically the extraction liquid is an alcohol. Preparedin this manner, compositions of the present invention may containbetween about 1 drop and about 30 drops of muira puama extract in fourounces of the topical composition. Preferably, the compositions of thepresent invention contain between about 5 drops and about 20 drops ofmuira puama extract in four ounces of the topical composition. Mostpreferably, the compositions of the present invention contain about 12drops of muira puama extract in four ounces of the topical composition.Herbal extracts of muira puama that are suitable for use in formulatingcompositions of the present invention are available commercially. Aconcentrated extract that is suitable for use in compositions of thepresent invention is commercially available from Raintree Nutrition.

Catuaba is a botanical extracted from the plant species Juniperisbrasilinsis native to Brazil. It is reported to have benefits inrelieving insomnia from hypertension, restless sleeping patterns and inhelping to arrest failing memory. The compositions of the presentinvention may include catuaba extract prepared by extracting one ounceof catuaba bark into two ounces of a suitable liquid. Typically theextraction liquid is water or an alcohol. Prepared in this manner,compositions of the present invention may contain between about 1 dropand about 30 drops of catuaba extract in four ounces of the topicalcomposition. Preferably, the compositions of the present inventioncontain between about 5 drops and about 20 drops of catuaba extract infour ounces of the topical composition. Most preferably, thecompositions of the present invention contain about 12 drops of catuabaextract in four ounces of the topical composition. Herbal extractscontaining catauba that are suitable for use in formulating compositionsof the present invention are available commercially. For example, acatuaba bark extract suitable for use in compositions of the presentinvention is commercially available from Raintree Nutrition.

Maca is a plant also known as Lepidium meyenii. Peruvian maca root is avegetable root or tuber related to the potato and the Mexican wild yam.It contains amino acids, complex carbohydrates, vitamins B1, B2, B12, Cand E and minerals, including calcium, phosphorus, zinc, magnesium andiron. This herb has traditionally been used to increase energy,vitality, stamina and endurance in athletes, promote mental clarity, asan aphrodisiac for both men and women, for male impotence, menstrualirregularities and female hormone imbalances, including menopause. Thecompositions of the present invention may include maca extract preparedby extracting one ounce of maca plant root material into two ounces of asuitable liquid. Typically the extraction liquid is water or an alcohol.Prepared in this manner, compositions of the present invention maycontain between about 1 drop and about 30 drops of maca extract in fourounces of the topical composition. Preferably, the compositions of thepresent invention contain between about 5 drops and about 20 drops ofmaca extract in four ounces of the topical composition. Most preferably,the compositions of the present invention contain about 12 drops of macaextract in four ounces of the topical composition. Maca plant materialsuitable for use in preparing extracts for use in formulatingcompositions of the present invention are available commercially. Forexample, bulk maca plant material that is suitable for use incompositions of the present invention is commercially available fromRaintree Nutrition.

Saw Palmetto is an urinary antiseptic also known as Serenoa repens. Thisherb acts to tone and strengthen the male reproductive system and isused in cases of enlarged prostate gland. The compositions of thepresent invention may include saw palmetto extract prepared byextracting the saw palmetto from one ounce of a plant materialcontaining the herb into two ounces of a suitable liquid. Typically theextraction liquid is water or an alcohol. Prepared in this manner,compositions of the present invention may contain between about 1 dropand about 30 drops of saw palmetto extract in four ounces of the topicalcomposition. Preferably, the compositions of the present inventioncontain between about 5 drops and about 20 drops of saw palmetto extractin four ounces of the topical composition. Most preferably, thecompositions of the present invention contain about 12 drops of sawpalmetto extract in four ounces of the topical composition. Herbalextracts containing saw palmetto that are suitable for use informulating compositions of the present invention are availablecommercially. For example, a saw palmetto extract that is suitable foruse in compositions of the present invention is commercially availablefrom Nature's Alternative.

The compositions of the present invention can optionally include asactive ingredients nettles and/or zinc. The components are widelyavailable commercially.

The compositions of the present invention may contain other ingredientsthat are not physiologically active but serve to enhance thepharmaceutical elegance of the final topical composition. For example,the compositions of the present invention may contain excipients such aslactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia,calcium silicate, microcrystalline cellulose, polyvinylpyrrolidinone,cellulose, water, syrup, and methyl cellulose. Additionally, thecompositions of the present invention may include lubricating agentssuch as talc, magnesium stearate and mineral oil, wetting agents,emulsifying and suspending agents, preserving agents such as methyl- andpropylhydroxybenzoates, sweetening agents or flavoring agents.

The compositions of the present invention may be formulated in anypharmaceutically acceptable topical vehicle that does not interactadversely with the active ingredients or, in the case of the embodimentwhich includes a coating of the compositions applied to one surface of acondom, does not interact adversely with the condom materials. Forexample, compositions of the present invention may be formulated inwater or oil based topical vehicles. These compositions can includelanolin, aquaphor, methylcellulose and derivatives thereof, petroleumbased vehicles, aloe and the like. Preferably, the compositions of thepresent invention are formulated in a topical, water-based vehiclecontaining aloe and vitamin E. Suitable topical vehicles containing aloeand vitamin E are available commercially. For example, a suitabletopical vehicle for use in formulating compositions of the presentinvention containing aloe and vitamin E is available from T. C.Laboratories (Treasures Company).

Preferably, the topical compositions of the present invention contain amixture of distilled water, aloe barbadensis leafjuice, helianthus annus(sunflower) seed oil, stearic acid, glycine soja (soybean) oil, cetylalcohol NF, emulsifying wax, olea Europaea (olive) fruit oil, glycerin,palmitic acid, cymbopogan schoenanthus (lemongrass) oil, mentha piperita(peppermint) oil, tocopherol, denatured alcohol, methyl salicylate, aloebarbadensis leaf extract, menthol, fragrance, camella sinensis (greentea) leaf extract, rosmarinus officinalis (rosemary) leaf extract,citrus grandis (grapefruit) seed extract, lecithin, sodium bicarbonate,ascorbyl palmitate, polysorbate 20, methylparaben, propylparaben, urticadioica (nettles) extract or zinc oxide, having a pH of between about 5.0and about 8.

The compositions of the present invention are formulated for transdermaldelivery of the active ingredients following topical administration tothe penis or labia inajora and minora pudendi. A small amount of thecompositions of the present invention is applied topically directly tothe penis or labia majora and minora pudendi. Alternatively, in apreferred embodiment, the composition may be packaged as a coating onthe interior surface of a condom. Thereby, upon use of the condom, thecomposition is applied topically to the penis.

EXAMPLES Example 1

A preferred embodiment of the topical compositions of the presentinvention consists essentially of the following ingredients of a qualityand purity suitable for topical application to a mammal: Activeingredient Amount per 30 g ± 10% methyl nicotinate 0.3 g yohimbe extract25 drops L-arginine 240 mg muira puama extract 12 drops catuaba barkextract 12 drops maca extract 12 drops saw palmetto 12 drops

These active ingredients were formulated in a base for topicaladministration in a pharmaceutically-acceptable topical vehiclecontaining distilled water, aloe barbadensis leaf juice, helianthusannus (sunflower) seed oil, stearic acid, glycine soja (soybean) oil,cetyl alcohol NF, emulsifying wax, olea Europaea (olive) fruit oil,glycerin, palmitic acid, cymbopogan schoenanthus (lemongrass) oil,mentha piperita (peppermint) oil, tocopherol, denatured alcohol, methylsalicylate, aloe barbadensis leaf extract, camella sinensis (green tea)leaf extract, rosmarinus officinalis (rosemary) leaf extract, citrusgrandis (grapefruit) seed extract, lecithin, sodium bicarbonate,ascorbyl palmitate, polysorbate 20, methylparaben, propylparaben, miticadioica (nettles) extract and zinc oxide, having a pH of about 6.0.

Example 2

A preferred embodiment of the topical compositions of the presentinvention consists essentially of the following ingredients of a qualityand purity suitable for topical application to a mammal: Activeingredient Amount per 30 g ± 10% methyl nicotinate 0.3 g L-arginine 240mg muira puama extract 12 drops catuaba bark extract 12 drops macaextract 12 drops

These active ingredients were formulated in a base for topicaladministration in a pharmaceutically-acceptable topical vehiclecontaining distilled water, aloe barbadensis leaf juice, helianthusannus (sunflower) seed oil, stearic acid, glycine soja (soybean) oil,cetyl alcohol, emulsifying wax, olea europaea (olive) fruit oil,glycerin, palmitic acid, fragrance, tocopherol, denatured alcohol,methyl salicylate, aloe barbadensis leaf extract, camella sinensis(green tea) leaf extract, rosmarinus officinalis (rosemary) leafextract, citrus grandis (grapefruit) seed extract, lecithin, sodiumbicarbonate, ascorbyl palmitate, polysorbate 20, menthol, methylparaben,propylparaben, urtica dioica (nettles) extract and zinc oxide, having apH of about 6.0.

The foregoing description of the present invention has been presentedfor purposes of illustration and description. Furthermore, thedescription is not intended to limit the invention to the form disclosedherein. Consequently, variations and modifications commensurate with theabove teachings, and the skill or knowledge of the relevant art, arewithin the scope of the present invention. The embodiment describedhereinabove is further intended to explain the best mode known forpracticing the invention and to enable others skilled in the art toutilize the invention in such, or other, embodiments and with variousmodifications required by the particular applications or uses of thepresent invention. It is intended that the appended claims be construedto include alternative embodiments to the extent permitted by the priorart.

1. A composition formulated for topical administration to a mammalconsisting of: a vasodilating composition consisting of methylnicotinate and methyl salicyclate, and a water-based topical vehiclecomprising water, aloe, green tea extract, a vegetable oil and at leastone compound selected from the group consisting of stearic acid, sodiumbicarbonate, cetyl alcohol, methyl paraben and propyl paraben.
 2. Thecomposition of claim 1, wherein the composition contains about 0.1%methyl nicotinate.
 3. The composition of claim 1, wherein the vegetableoil is selected from the group consisting of soybean oil and sunfloweroil.
 4. The composition of claim 1, wherein the water-based topicalvehicle further comprises at least one of ascorbyl palmitate andtocopherol acetate.
 5. A composition formulated for topicaladministration to a mammal consisting of: a vasodilating compositionconsisting of L-arginine, methyl nicotinate and methyl salicyclate; and,a water-based topical vehicle comprising water, aloe, green tea extract,a vegetable oil and at least one compound selected from the groupconsisting of stearic acid, sodium bicarbonate, cetyl alcohol, methylparaben and propyl paraben.
 6. The composition of claim 1, wherein thecomposition contains about 0.1% methyl nicotinate.
 7. The composition ofclaim 1, wherein the vegetable oil is selected from the group consistingof soybean oil and sunflower oil.
 8. The composition of claim 1, whereinthe water-based topical vehicle further comprises at least one ofascorbyl palmitate and tocopherol acetate.
 9. A condom having aninternal surface coating comprising a topical composition consisting of:a vasodilating composition consisting of methyl nicotinate and methylsalicyclate, and a water-based topical vehicle comprising water, aloe,green tea extract, a vegetable oil and at least one compound selectedfrom the group consisting of stearic acid, sodium bicarbonate, cetylalcohol, methyl paraben and propyl paraben.
 10. A method of enhancingsexual response in a mammal comprising topically applying a compositionconsisting of: a vasodilating composition consisting of methylnicotinate and methyl salicyclate, and a water-based topical vehiclecomprising water, aloe, green tea extract, a vegetable oil and at leastone compound selected from the group consisting of stearic acid, sodiumbicarbonate, cetyl alcohol, methyl paraben and propyl paraben, to thegenitalia of a mammal in need of such treatment.